Long-term Survival after Volatile or Propofol General Anesthesia for Bladder Cancer Surgery: A Retrospective National Registry Cohort Study.

BACKGROUND: Prospective interventional trials and retrospective observational analyses provide conflicting evidence regarding the relationship between propofol versus inhaled volatile general anesthesia and long-term survival after cancer surgery. Specifically, bladder cancer surgery lacks prospective clinical trial evidence. METHODS: Data on bladder cancer surgery performed under general anesthesia between 2014 and 2021 from the National Quality Registry for Urinary Tract and Bladder Cancer and the Swedish Perioperative Registry were record-linked. Overall survival was compared between patients receiving propofol or inhaled volatile for anesthesia maintenance. The minimum clinically important difference was defined as a 5-percentage point difference in 5-yr survival. RESULTS: Of 7,571 subjects, 4,519 (59.7%) received an inhaled volatile anesthetic, and 3,052 (40.3%) received propofol for general anesthesia maintenance. The two groups were quite similar in most respects but differed in American Society of Anesthesiologists Physical Status and tumor stage. Propensity score matching was used to address treatment bias. Survival did not differ during follow-up (median, 45 months [interquartile range, 33 to 62 months]) in the full unmatched cohort nor after 1:1 propensity score matching (3,052 matched pairs). The Kaplan-Meier adjusted 5-yr survival rates in the matched cohort were 898 of 3,052, 67.5% (65.6 to 69.3%) for propofol and 852 of 3,052, 68.5% (66.7 to 70.4%) for inhaled volatile general anesthesia, respectively (hazard ratio, 1.05 [95% CI, 0.96 to 1.15]; P = 0.332). A sensitivity analysis restricted to 1,766 propensity score-matched pairs of patients who received only one general anesthetic during the study period did not demonstrate a difference in survival; Kaplan-Meier adjusted 5-yr survival rates were 521 of 1,766, 67.1% (64.7 to 69.7%) and 482 of 1,766, 68.9% (66.5 to 71.4%) for propofol and inhaled volatile general anesthesia, respectively (hazard ratio, 1.09 [95% CI, 0.97 to 1.23]; P = 0.139). CONCLUSIONS: Among patients undergoing bladder cancer surgery under general anesthesia, there was no statistically significant difference in long-term overall survival associated with the choice of propofol or an inhaled volatile maintenance.

Cumulative incidence of and risk factors for BCG infection after adjuvant BCG instillations.

OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

The Risk of Thromboembolism in Patients with Muscle Invasive Bladder Cancer before and after Cystectomy Depending on Blood Group and Neoadjuvant Chemotherapy-A Multicentre Retrospective Cohort Study.

PURPOSE: Previous studies have indicated that patients with muscle-invasive bladder cancer with non-O blood types have an increased risk of experiencing thromboembolic events (TEEs). This is finding is in relation to neoadjuvant-chemotherapy (NAC)-naïve patients. AIM: to establish the risk of TEEs and any association with blood types among NAC patients as well as NAC-naïve patients. METHODS: Cystectomized patients at four centres treated from 2009 to 2018 (n = 244) were analysed. The quantities of patients corresponding to each blood group were as follows: A-108 (44%); O-99 (41%); B-30 (12%); and AB-7 (3%). NAC patients (n = 167) and NAC-naïve NAC-eligible patients (n = 77) were assessed. In total, 54 women (22%) and 190 men (78%), with a median age of 69 years, were included in the study. The occurrence of any type of TEE from six months pre-cystectomy to 12-24 months after was analysed using logistic regression adjusted for NAC and confounders. RESULTS: Sixty-six TEEs were detected in 21% of the patients (n = 52). Pulmonary embolus (n = 33) and deep venous thrombosis (n = 11) were the most common forms. No significant differences between blood types were found in the analysis, although B blood type had a nearly significant increased crude risk compared with O blood type, for which there was an OR of 2.48 (95% CI 0.98-6.36). Adjustment for NAC and covariates weakened the OR, which plummeted to 1.98 (95% CI 0.71-5.51). CONCLUSIONS: No significant associations were found between blood types and TEE occurrences in this cohort including both NAC and NAC-naïve NAC-eligible patients.

Long-term patient follow-up should be routinely implemented in radiotherapy units to detect late adverse effects after cancer treatment.

Editorial comment to Urosymphyseal fistula after pelvic radiotherapy - an entity in patients with significant comorbidity requiring multidisciplinary management Scand J Urol. 2023.

A Validation Study of cT-Categories in the Swedish National Urinary Bladder Cancer Register-Norrland University Hospital.

BACKGROUND: In Sweden, all patients with urinary bladder cancer (UBC) are recorded in the Swedish National Register for Urinary Bladder Cancer (SNRUBC). The purpose of this study was to validate the registered clinical tumour categories (cT-categories) in the SNRUBC for Norrland University Hospital, Sweden, from 2009 to 2020, inclusive. METHODS: The medical records of all 295 patients who underwent radical cystectomy for the treatment of UBC were reviewed retrospectively. Possible factors impacting the cT-categories were identified. To optimise cT-classification, computed tomography urography of all patients with suspected tumour-associated hydronephrosis (TAH) or suspected tumour in bladder diverticulum (TIBD) were retrospectively reviewed by a radiologist. Discrepancy was tested with a logistic regression model. RESULTS: cT-categories differed in 87 cases (29.5%). Adjusted logistic regression analysis found TIBD and TAH as significant predictors for incorrect registration; OR = 7.71 (p < 0.001), and OR = 17.7, (p < 0.001), respectively. In total, 48 patients (68.6%) with TAH and 12 patients (52.2%) with TIBD showed discrepancy regarding the cT-category. Incorrect registration was mostly observed during the years 2009-2012. CONCLUSION: The study revealed substantial incorrect registration of cT-categories in SNRUBC. A major part of the misclassifications was related to TAH and TIBD. Registration of these variables in the SNRUBC might be considered to improve correct cT-classification.

Immune-Activated B Cells Are Dominant in Prostate Cancer.

B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19+ B-cell compartment was significantly decreased in PCa patients and dominated by naïve B cells. The nodal B-cell compartment had significantly increased fractions of CD19+ B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.

Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed. METHODS: Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae. RESULTS: BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients. CONCLUSIONS: The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value.

Short term outcomes after robot assisted and open cystectomy - A nation-wide population-based study.

INTRODUCTION: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population. MATERIALS AND METHODS: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary outcomes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models. RESULTS: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multivariable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0). CONCLUSION: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.

Thromboembolic Events in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Study of Renal Impairment in Relation to Potential Thromboprophylaxis.

Recent studies on patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC) have shown an association between NAC and thromboembolic events (TEE) prior to radical cystectomy (RC). Recent studies suggest that central venous access catheters (CVAs) may induce TEEs, and low-molecular-weight heparin (LMWH) has been mentioned as possible prophylaxis. However, other studies have shown a high incidence of decreased renal function in these patients. The purpose of this study was to determine the portion of MIBC patients with NAC-induced TEEs who had decreased preoperative renal function for whom LMWH potentially would not be beneficial as prophylaxis. We identified 459 cystectomized MIBC patients from two Swedish medical centers from 2009 to 2021. The inclusion criterion of cT2-T4aN0M0 resulted in 220 eligible patients, who were further divided into NAC-administered (n = 187) and NAC-eligible (n = 33), the tentative control group. Values of renal function before, during, and after each NAC cycle were retrospectively collected from individual medical records. Amongst the NAC-administered patients with TEE (n = 29), 41% (95% CI 23.5-61.1%) of patients had decreased renal function. Thus, a substantial portion of NAC-administered patients who developed TEEs had reduced renal function and would have been less likely to have benefited from renal clearance-dependent LMWH prophylaxis.

A Retrospective Analysis of the De Ritis Ratio in Muscle Invasive Bladder Cancer, with Focus on Tumor Response and Long-Term Survival in Patients Receiving Neoadjuvant Chemotherapy and in Chemo Naïve Cystectomy Patients-A Study of a Clinical Multicentre Database.

Background: A high pre-treatment De Ritis ratio, the aspartate transaminase/alanine aminotransferase ratio, has been suggested to be of prognostic value for mortality in muscle-invasive bladder cancer (MIBC). Our purpose was to evaluate if a high ratio was associated with mortality and downstaging. Methods: A total of 347 Swedish patients with clinically staged T2-T4aN0M0, with administered neoadjuvant chemotherapy (NAC) or eligible for NAC and undergoing radical cystectomy (RC) 2009−2021, were retrospectively evaluated with a low ratio < 1.3 vs. high ratio > 1.3, by Log Rank test, Cox regression and Mann−Whitney U-test (MWU), SPSS 27. Results: Patients with a high ratio had a decrease of up to 3 years in disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) (p = 0.009, p = 0.004 and p = 0.009) and 5 years in CSS and OS (p = 0.019 and p = 0.046). A high ratio was associated with increased risk of mortality, highest in DFS (HR, 1.909; 95% CI, 1.265−2.880; p = 0.002). No significant relationship between downstaging and a high ratio existed (p = 0.564 MWU). Conclusion: A high pre-treatment De Ritis ratio is on a population level, associated with increased mortality post-RC in endpoints DFS, CSS and OS. Associations decrease over time and require further investigations to determine how strong the associations are as meaningful prognostic markers for long-term mortality in MIBC. The ratio is not suitable for downstaging-prediction.

Number of transurethral procedures after non-muscle-invasive bladder cancer and survival in causes other than bladder cancer.

BACKGROUND: Previous research has associated repeated transurethral procedures after a diagnosis of non-muscle invasive bladder cancer (NMIBC) with increased risk of death of causes other than bladder cancer. AIM: We investigated the overall and disease-specific risk of death in patients with NMIBC compared to a background population sample. METHODS: We utilized the database BladderBaSe 2.0 containing tumor-specific, health-related and socio-demographic information for 38,547 patients with NMIBC not primarily treated with radical cystectomy and 192,733 individuals in a comparison cohort, matched on age, gender, and county of residence. The cohorts were compared using Kaplan-Meier curves and Hazard ratios (HR) from a Cox regression models. In the NMIBC cohort, we analyzed the association between number of transurethral procedures and death conditioned on surviving two or five years. RESULTS: Overall survival and survival from causes other than bladder cancer estimated with Kaplan-Meier curves was 9.3% (95% confidence interval (CI) (8.6%-10.0%)) and 1.4% (95% CI 0.7%-2.1%) lower respectively for the NMIBC cohort compared to the comparison cohort at ten years. In a Cox model adjusted for prognostic group, educational level and comorbidity, the HR was 1.03 (95% CI 1.01-1.05) for death from causes other than bladder cancer comparing the NMIBC cohort to the comparison cohort. Among the NMIBC patients, there was no discernible association between number of transurethral procedures and deaths of causes other than bladder cancer after adjustment. The number of procedures were, however, associated with risk of dying from bladder cancer HR 3.56 (95% CI 3.43-3.68) for four or more resections versus one within two years of follow-up. CONCLUSION: The results indicate that repeated diagnostic or therapeutic transurethral procedures under follow-up do not increase of risk dying from causes other than bladder cancer. The modestly raised risk for NMIBC patients dying from causes other than bladder cancer is likely explained by residual confounding.

Adverse events during neoadjuvant chemotherapy for muscle invasive bladder cancer-a Swedish retrospective multicentre study of a clinical database.

Background: Adverse events (AEs) during neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC) are known but insufficiently reported. Clinical implications include affected cardiac, pulmonary, urinary, vascular and haematological organ systems. The main purpose was to evaluate the incidence and severity of AEs for ascertaining possible clinical significance. Further investigating possible effects of AEs on downstaging outcomes-downstaging is considered a surrogate marker for overall survival (OS). Methods: A retrospective evaluation of AEs during ongoing NAC for MIBC patients analysing individual patient data in a clinical database. We identified 687 cystectomies between 2009-2020 at four Swedish urological centres. Inclusion criteria were cT2-4aN0M0 in 261 NAC patients undergoing radical cystectomy (RC). Medical files were reviewed and AEs were assessed and graded, including detailed measurements by the Common Terminology Criteria for Adverse Events (CTCAE) v.5. Data were retrospectively analysed in SPSS statistics 27.0 with Spearman rank-order correlation coefficient and Mann-Whitney U-test (MWU). Results: A total of 251/261 patients [95% confidence interval (CI), 93-98%] experienced AEs during NAC pre-RC (mean two AEs/patient). In total, 208 (80%) patients received methotrexate, vinblastine, adriamycin (doxorubicin) and cisplatin (MVAC). In the total cohort, 200 (76.6%) received all pre-planned NAC-cycles. Most common AEs were anaemia (88.9%), thrombocytopenia (44.8%) and acute kidney injury (40.6%). Patients with prematurely terminated cycles had higher AE-grades (P=0.042 MWU). A correlation between higher AE-grades and decrease in downstaging existed, in the entire cohort (-0.133; P=0.033) and in patients undergoing all pre-planned NAC-cycles (-0.148; P=0.038). Anaemia and acute kidney injury were individually associated with decreased downstaging (-0.360, P=0.025 and -0.183, P=0.010, respectively). Conclusions: NAC in MIBC poses a significant risk for AEs before RC with clinical implications. For instance, patients terminating chemotherapy prematurely, have higher AE-grades and decreased downstaging. Further, acute kidney injury and anaemia are individually associated with decreased downstaging. We propose that early detection and prevention of AEs may increase downstaging of the primary tumour.

Central Venous Access and the Risk for Thromboembolic Events in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer.

Thromboembolic events (TEE) are high-risk complications in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for urothelial muscle-invasive bladder cancer (MIBC). The purpose of the study was to investigate any differences in TEE-incidence, comparing peripherally inserted central catheter (PICC) versus a totally implanted port (PORT) as CVA (central venous access) during NAC. We identified 947 cystectomized MIBC-patients from four Swedish medical centers in 2009-2021. Inclusion criteria were cT2-T4aN0M0 and 375 patients were finally eligible and evaluated, divided into: NAC-administered (n = 283) resp. NAC-naïve-NAC-eligible (n = 92), the latter as tentative control group. Data on TEEs and types of CVA were retrospectively collected and individually validated, from final transurethral resection of the bladder tumor (TUR-B) to 30 days post-RC. Adjusted logistic regression and log rank test were used for statistical analyses. Amongst NAC-administered, 83% (n = 235) received PICCs and 15% (n = 42) PORTs. Preoperative TEEs occurred in 38 PICC-patients (16.2%) and in one PORT-patient (2.4%), with 47 individual events registered. We found a significantly increased odds ratio of TEE in NAC-administered PICC-patients compared to in PORT-patients (OR: 8.140, p-value: 0.042, 95% CI 1.078-61.455). Our findings indicate a greater risk for pre-RC TEEs with PICCs than with PORTs, suggesting favoring the usage of PORTs for MIBC-NAC-patients.

Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience.

OBJECTIVES: To compare time intervals to diagnosis and treatment, tumor characteristics, and management in patients with primary urinary bladder cancer, diagnosed before and after the implementation of a standardized care pathway (SCP) in Sweden. MATERIALS AND METHODS: Data from the Swedish National Register of Urinary Bladder Cancer was studied before (2011-2015) and after (2016-2019) SCP. Data about time from referral to transurethral resection of bladder tumor (TURBT), patients and tumor characteristics, and management were analyzed. Subgroup analyses were performed for cT1 and cT2-4 tumors. RESULTS: Out of 26,795 patients, median time to TURBT decreased from 37 to 27 days after the implementation of SCP. While the proportion of cT2-T4 tumors decreased slightly (22-21%, p < 0.001), this change was not stable over time and the proportions cN + and cM1 remained unchanged. In the subgroups with cT1 and cT2-4 tumors, the median time to TURBT decreased and the proportions of patients discussed at a multidisciplinary team conference (MDTC) increased after SCP. In neither of these subgroups was a change in the proportions of cN + and cM1 observed, while treatment according to guidelines increased after SCP in the cT1 group. CONCLUSION: After the implementation of SCP, time from referral to TURBT decreased and the proportion of patients discussed at MDTC increased, although not at the levels recommended by guidelines. Thus, our findings point to the need for measures to increase adherence to SCP recommendations and to guidelines.

Swedish National Guidelines on Urothelial Carcinoma: 2021 update on non-muscle invasive bladder cancer and upper tract urothelial carcinoma.

OBJECTIVE: To overview the updated Swedish National Guidelines on Urothelial Carcinoma 2021, with emphasis on non-muscle-invasive bladder cancer (NMIBC) and upper tract urothelial carcinoma (UTUC). METHODS: A narrative review of the updated version of the Swedish National Guidelines on Urothelial Carcinoma 2021 and highlighting new treatment recommendations, with comparison to the European Association of Urology (EAU) guidelines and current literature. RESULTS: For NMIBC the new EAU 2021 risk group stratification has been introduced for non-muscle invasive bladder cancer to predict risk of progression and the web-based application has been translated to Swedish (https://nmibc.net.). For patients with non-BCG -responsive disease treatment recommendations have been pinpointed, to guide patient counselling in this clinical situation. A new recommendation in the current version of the guidelines is the introduction of four courses of adjuvant platinum-based chemotherapy to patients with advanced disease in the nephroureterectomy specimen (pT2 or higher and/or N+). Patients with papillary urothelial neoplasms with low malignant potential (PUNLMP) can be discharged from follow-up already after 3 years based on a very low subsequent risk of further recurrences. CONCLUSIONS: The current version of the Swedish national guidelines introduces a new risk-stratification model and follow-up recommendation for NMIBC and adjuvant chemotherapy after radical surgery for UTUC.

Bladder cancer recurrence in papillary urothelial neoplasm of low malignant potential (PUNLMP) compared to G1 WHO 1999: a population-based study.

OBJECTIVE: Papillary urothelial neoplasm of low malignant potential (PUNLMP) and stage TaG1 non-muscle invasive bladder cancer (NMIBC) represent separate categories in current WHO 1999 grade definitions. Similarly, PUNLMP and Ta low-grade are separate entities in the WHO 2004/2016 grading system. However, this classification is currently questioned by reports showing a similar risk of recurrence and progression for both categories. PATIENTS AND METHODS: In this population-based study, risk estimates were evaluated in patients diagnosed with PUNLMP (n = 135) or stage TaG1 (n = 2176) NMIBC 2004-2008 with 5-year follow-up registration in the nation-wide Bladder Cancer Data Base Sweden (BladderBaSe). The risk of recurrence was assessed using multivariable Cox regression with adjustment for multiple confounders (age, gender, marital status, comorbidity, educational level, and health care region). RESULTS: At five years, 28/135 (21%) patients with PUNLMP and 922/2176 (42%) with TaG1 had local recurrence. The corresponding progression rates were 0.7% (1/135) and 4.0% (86/2176), respectively. A higher relative risk of recurrence was detected in patients with TaG1 tumours compared to PUNLMP (Hazard Ratio 1.6, 95% CI 1.2-2.0) at 5-year follow-up, while progression events were too few to compare. CONCLUSIONS: The difference in risk of recurrence between primary stage TaG1 and PUNLMP stands in contrast to the recently adapted notion that treatment and follow-up strategies can be merged into one low-risk group of NMIBC.

Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer.

INTRODUCTION AND OBJECTIVES: Bladder cancer is primarily a disease of older age and little is known about the differences between patients diagnosed with bladder cancer at a younger versus older age. Our objectives were to compare bladder cancer specific survival in patients aged <50 versus those aged 50-70 at time of diagnosis. MATERIALS AND METHODS: The Swedish bladder cancer database provided data on patient demographics, clinical characteristics and treatments for this observational study. Cox proportional hazard regression models were adjusted for appropriate variables. All analyses were stratified by disease stage (non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Furthermore, we compared the frequency of lower urinary tract infections within 24 months prior to bladder cancer diagnosis by sex and age groups. RESULTS: The study included 15,452 newly-diagnosed BC patients (1997-2014); 1,207 (8%) patients were <50 whilst 14,245 (92%) were aged 50-70. Patients aged <50 at diagnosis were at a decreased risk of bladder cancer death (HR = 0.82, 95%CI: 0.68-0.99) compared to those aged 50-70. When stratified by non-muscle-invasive and muscle-invasive bladder cancer, this association remained in non-muscle-invasive patients only (<50, HR = 0.43, 95% CI: 0.28-0.64). The frequency of lower urinary tract infection diagnoses did not differ between younger and older patients in either men or women. CONCLUSIONS: Patients diagnosed with non-muscle-invasive bladder cancer when aged <50 are at decreased risk of bladder cancer-specific death when compared to their older (50-70) counterparts. These observations raise relevant research questions about age-related differences in diagnostic procedures, clinical decision-making and, not least, potential differences in tumour biology.

A prospective multicenter study of visual response-evaluation by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer.

PURPOSE: To evaluate a method of transurethral visual response-staging in patients with urothelial muscle-invasive urinary bladder cancer (MIBC), undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). METHODS: A prospective study at four Swedish cystectomy centers, cystoscopy was performed after final NAC-cycle for MIBC. Fifty-six participants underwent cystoscopy for visual staging of the tumor immediately pre-RC. Visual assessments were correlated to pathoanatomical outcomes post-RC. RESULTS: Seventeen tumors were classified as complete response (CR), i.e. pT0. Twenty-five patients had residual MIBC and 14 had non-muscle invasive residual tumors (NMIBC). Of the 39 patients with residual tumor, 25 were correctly identified visually (64%). Eleven patients were pN+. The diagnostic accuracy of cystoscopy to correctly identify complete response or remaining tumor was 70% (CI = 56-81%) with a sensitivity of 64% (CI = 47-79%), specificity 82% (CI = 57-96%), PPV 89% (CI = 74-96%) and NPV 50% (CI =38-61%). Twenty-eight cystoscopy evaluations showed signs of residual tumors and 3/28 (11%) were false positive. In 4/14 patients assessed having residual NMIBC the estimates were correct, 8/14 had histopathological MIBC and 2/14 had CR. In 11/14 patients (79%), the suggested visual assessment of MIBC was correct, 2/14 had NMIBC and 1/14 had CR. Twenty-eight cystoscopies had negative findings, 14 were false negatives (50%), when cystoscopy falsely predicted pT0. Among them there were eight patients with pTa, pT1 or pTis and six MIBC-tumors. In 17 patients with histopathological pT0, 14 were correctly identified with cystoscopy (82%). CONCLUSION: Cystoscopy after the final NAC-cycle cannot robustly differentiate between NAC-responders and non-responders. Visually, negative MIBC-status cannot be determined safely.

Nomograms including the UBC® Rapid test to detect primary bladder cancer based on a multicentre dataset.

OBJECTIVES: To evaluate the clinical utility of the urinary bladder cancer antigen test UBC® Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. PATIENTS AND METHODS: Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC® Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC® Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. RESULTS: The sensitivity, specificity, and area under the curve for the UBC® Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58-0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70-0.76) for high-grade (HG) BC, respectively. Age, UBC® Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72-0.87) and 0.95 (95% CI: 0.92-0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC® Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. CONCLUSION: The UBC® Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC.